In this course we will study the role of the different key constituents of the translation machinery in cells, and the essential importance of the Genetic Code in the generation of active proteins. At the practical side, we will learn the common laboratory techniques used for protein expression and purification in a prokaryotic system (Escherichia coli), and also certain specific techniques to introduce mutations in the sequence of genes to produce recombinant proteins with modified functions.

3. Chemical synthesis of bioactive molecules 

Marta Frigolé (Laboratory of Molecular Biophysics)

Chemistry is at the heart of the drug-discovery process. For each new drug reaching the market, there have been billions of compounds synthesised and tested. Why so many? Because is by chemically modulating the structure of the molecules that we can fine-tune their potency and also their pharmacodynamic/pharmacokinetic properties (absorption, distribution, metabolism, excretion and side-effects).

In this practical course we will synthesise acetaminophen, also known as paracetamol or the active ingredient in Gelocatil®. While doing so we will learn how chemists plan and design the synthesis routes as well as the main techniques and instruments used to build the active ingredients of all small-molecule drugs.

4. Meet the guardians of the DNA

Josep Biayna (Genome Data Science)

Marina Villamor (Genomic Instability and Cancer Laboratory)

Our DNA can break due to external (i.e. the sun and chemical agents) and internal (i.e. DNA replication) factors. To solve this problem, we have some genes that function as the guardians of our genome, by identifying these lesions and activating the DNA Damage Response (DDR) pathway. However, the DDR pathway does not always work properly. If the damage is severe, the cell undergo to apoptosis (programmed cell death) or senescence (permanent cell cycle arrest). On the other hand, if the stability of the genome is not massively compromised, the cell survives and starts proliferating in an uncontrolled manner. The transformation of a normal cell into a tumour cell is a multi-step process that involves dynamic changes in the genome at both the genetic and epigenetic levels. Currently, cancer accounts for 8 million deaths per year, being the most common cause of death in Europe after cardiovascular diseases.

Our lab is interested in deciphering the potential role of genomic instability and the DDR in cancer predisposition. In this practical course, we will monitor the effect of DNA damage in different cancer cell lines and perform some techniques that are daily used in the lab to study this phenomenon. 

5. Targeting the Tumour Microenvironment in colorectal cancer metastasis

Jordi Badia (Colorectal cancer laboratory)

Colorectal Cancer (CRC) is the most common cancer and the second leading cause of cancer-related deaths in Spain, according to the AECC (Asociación Española Contra el Cáncer). CRC produces cancers in the large intestine through a multi-step process that, like many other types of cancer, starts with the acquisition of mutations in key genes. These mutations then go on to make cells proliferate without control. CRC can be easily treated if detected early. However, we still need to find effective treatments for the most advanced stages of cancer, particularly for metastasis—the final and deadliest step of cancer, which in the case of CRC occurs mainly in the liver.

The great potential of cancer cells resides not only in their capacity for mass proliferation but also in their ability to trick the healthy cells surrounding them. Fibroblasts, cells of the immune system, and blood vessels form what we call the tumour microenvironment (TME), which protects cancer cells from being removed and facilitates their invasion of other healthy organs. Our laboratory has recently shown that the TME is crucial for the aggressiveness of CRC and formation of metastasis in the liver. We are now channelling efforts into studying the potential of the TME as a way to block metastasis and into identifying novel treatments.

In this practical course we will provide an overview of several in vivo models and histological tools. Using these tools, we will discover and target those cells that form the TME of liver metastasis, with the aim to learn how to exploit them and stop the CRC metastasis. 

6. Targeting cell signaling pathways to treat cancer 

Lorena González  (Signalling and Cell Cycle Laboratory)

Cells have to constantly deal with changes in their extracellular environment. It means that they have to respond efficiently to these changes in order to prevent damage but also they have to control proliferation, survival and migration. To do that, cells have developed several mechanisms that allow them to receive, integrate and interpret signals to produce the appropriate response. These mechanisms, called ‘signaling pathways’, are based in a series of chemical changes. One of the most important modifications is phosphorylation and proteins which are able to phosphorylate others are called kinases.

Our laboratory is mainly focused in a particular protein kinase called p38 MAPK, which is activated under different stress situations and plays a critical role in inflammation, cell growth, proliferation, differentiation and cell death. However, when this pathway is dysregulated diseases such as cancer can arise. In that case, p38 MAPK inhibition could be beneficial to treat patients.

In this practical course we will provide an overview of the p38 MAPK signaling pathway and which are the main techniques we use in the lab to study it. We will use purified proteins and cultured cell lines to learn how p38 MAPK inhibitors work. Finally, we will explore which patients could benefit from them.

SEMESTER 2

1. The Role of Microtubules in Cell Division and Cancer

Joel Paz Domínguez (Microtubule organization)

Cellular cytoskeleton is perhaps one of the most important structures of the cell as it is involved in several functions as morphogenesis, cellular division or cell migration. It is composed by three members, actin filaments, intermediate filaments and microtubules. Microtubules are hollow cylindric polymers composed by tubulin dimers. Microtubules are very dynamic structures that constantly undergo episodes of polymerization and depolimerization which is known as dynamic instability. Microtubules are involved in key processes as intracellular transport of cargos (proteins, vesicles and even organelles) and in mitosis where they are in charge of the formation of the mitotic spindle and proper chromosome segregation. One of the hallmarks of cancer is uncontrolled cell division and one approach to treat cancer is to try to kill cancer cells. Compounds that target microtubules disrupting the normal cell division cycle and eventually lead to cell death have been proven to be one of the most effective cancer chemotherapeutic drugs available.

In this practical course, we will learn how a mitosis occurs in vivo, what are the different phases of mitosis, what is the role of microtubules in this process and how can we treat cancer focusing on microtubules. For this purpose, we will use cultured cell lines treated with several chemotherapeutic drugs used in cancer therapy and see how they affect cell division with the help of fluorescence light microscopy techniques.

2. Regulation of gene expression or why we don't understand our genome (yet)

Manuel Cañete (Translational control of cell cycle and differentiation)

In the year 2000, the Human Genome Project was completed at a cost of around 3 billion dollars and ten years of intense work. The main conclusion was that over 98% of our genetic material was junk DNA. Far from resolving our questions, by reading our genome it became apparent that we didn't understand it. Since then, mounting evidence has made us realise that understanding our genome means understanding how its expression is regulated.